Routes of administration of drugs are commonly administered via topical, enteral (via the digestive tract), parenteral routes (injection or infusion). Topical generally refers to, but is not limited to epicutaneous, inhalational, intranasal, vaginal, ocular surface and ear drops. Enteral generally refers to, but is not limited to the digestive tract, oral cavity, gastric cavity, and rectal administration. Parenteral generally refers to, but is not limited to administration by injection or infusion via intravenous, intrarterial, intramuscular, subcutaneous, transdermal, transmucosal, intradermal, intrathecal, intraosseous, intracardiac, interperitoneal, intravitreal, and inhalational.
RNA is emerging as an important drug target and versatile therapeutic agent because it folds into complex 3-D structures capable of expressing many enzymatic activities and because it “digitally” interferes with the flow of genetic information from DNA to proteins. Recent studies demonstrated that RNA also constitutes an attractive material for nanotechnology because RNA molecules can be easily programmed to carry out specific functions through the incorporation of aptamers. These novel “smart” macromolecules can be selected from random pools of RNA molecules based on their ability to bind metals, small organic compounds, nucleic acids, proteins and even entire cells and to change their inherent resistance to degradation for our benefit.
Aptamers can be produced by a conceptually straightforward two-step process that involves in vitro synthesis of more than 1015 individual RNA molecules and screening them by column affinity chromatography. This approach is commonly known as in vitro selection or Systemic Evolution of Ligands by EXpotential enrichment (SELEX). Although RNA is sensitive to degradation by ribonucleases (RNases), its stability can be easily regulated by incorporation of modified nucleotides. For example, incorporation of fluorine-CTP and -UTP (Epicentre Bio-technologies) makes RNA resistant to degradation by ubiquitous RNase A.
Another group of “smart” RNA molecules, ribozymes, are able to catalyze fundamental biological processes such as the synthesis of proteins (transpeptidation), aminoacylation of tRNA molecules (esterification), and RNA cleavage (transesterification). Their discovery has changed our views of macromolecular evolution, recognizing the fact that an informational molecule can simultaneously possess enzymatic activity. Ribozymes have now been described in a number of systems from bacteria through humans. The ubiquity of catalytic RNAs has prompted intensive investigation into potential applications as well as the mechanism of catalysis. The catalytic performance of nucleic acids can be enhanced by the incorporation of additional functional groups. A number of new ribozymes was discovered using SELEX.